The general problem with which we are concerned is the elucidation of cellular mechanisms of gene regulations which relate to the neoplastic process in humans. The phenomenon of ectopic protein synthesis in human cancer offers a good experimental model for investigating the problem. The ectopic synthesis of placental proteins by non-trophoblastic neoplasms is of special interest because of the frequent association of similar characteristics in neoplastic cells and embryonic cells. This has suggested that there may be a link between the mechanisms associated with the derepression of the genes synthesizing embryonic proteins and those involved in neoplastic transformation. We are conducting experiments in two fundamental categories. (1) Proof of ectopia: These studies are designed to test the assumption that the placental proteins are indeed synthesized by non-trophoblastic tumors and the assumption that they are coded for by the same genes as their normal counterparts. Chemical structure of the ectopic and placental proteins are being compared by seveal methods to determine whether they are the same. (2) Studies on the regulation of gene expression in normal and neoplastic cells: In these studies we measre and compare patterns of synthesis of placental proteins in normal trophoblast, in choriocarcinoma and in non-trophoblastic tumors to determine whether similar regulatory mechanisms are operant. These experiments are performed using tissue cultures derived from trophoblasts and from tumors which synthesize placental proteins especially. We have developed cell lines and have used them in the establishment of human/mouse hybrids for genetic analysis. In these investigations we are specifically studying the membrane glycoproteins of the placenta and their expression in cell lines derived from human neoplasms. BIBLIOGRAPHIC REFERENCES: Luduena, M.A. and Sussman, H.H. Characterization of KB cell alkaline phoshatase. Evidence of similarity to placental alkaline phosphatase. J. Biological Chemistry 251:2620-2628, May 1976. Badger, K.D. and Sussman, H.H. Structural evidence that human liver and placental alkaline phosphatase isoenzymes are coded by different genes. Proc. Nat'l. Acad. Sci. U.S.A. 73:2201-2205, July 1976.